Extracellular Immunity Flashcards
Explain why parasites provide a very difficult challenge to the immune system
- most are extracellular + too big for phagocytosis
- Thick coat = not penetrated by complement or T cell perforins
- Need to target weak spots
What is the main factor that drives extracellular immune responses?
Th2
Describe the Th2 immune response at mucosal surface
- Damage to epithelial cells (e.g. caused by worms)= release of ‘alarmins’ from epithelial cells that instruct DCs to promote Th2 response
- DCs take up + process worm Ags for presentation on MHC class II
- DCs migrate from tissue to lymph node + present antigen to CD4 T cells
Explain how a Th2 response is induced?
- Ag recognition leads to clonal expansion of T cells + differentiation towards Th2 lineage
- signals received by DCs in infected tissue promote Th2 responses
- Induction of Th2 response also requires IL-4- NOT produced by DCs
How is IL-4 produced to trigger a Th2 response?
Innate lymphoid cells (ILCs) can respond to alarmins by producing IL-4 + IL-13
- don’t express TCR/ BCR, don’t depend on recognition of specific Ag for activation
What are the different roles of ILC-derived IL-4 + IL-13?
- IL-4 supports differentiation of Th2 cells
- IL-13 can promote migration of DCs to lymph nodes
What does Th2-derived IL-4 do?
Mediates class switching to IgE or IgG1
What role do IgE and IgG1 play in extracellular immunity?
- IgE = mast cell degranulation, Eosinophil ‘Ab dependent cellular cytotoxicity’ (ADCC)
- IgG1 = immune cell degranulation, enhanced phagocytosis, ADCC, trapping of tissues migrating larvae by macrophages
Describe the effect of Th2 cytokines on intestinal epithelium
- Goblet cell hyperplasia/ > mucus production
- > production of resistin-like molecule-B = inhibits ability of worms to feed on host tissues during infection- < fecundity
Explain how the epithelial escalator + ‘Weep and Sweep’ contributes to extracellular immunity
- IL-13 stimulates >epithelial turnover (epithelial escalator)
- Th2 cytokines + mast cell proteases > fluid leakage across epithelium- IL-13 drives > intestinal muscle hypercontractility (weep + sweep)
What physiological changes are causes by anti-worm immunity
- Makes GI tract inhospitable for worms/ parasites
- > goblet cells resulting in >mucin/ intestinal mobility/ water influx into intestinal lumen
What does a Th2 response cause?
- alternative activation of macrophages (block Th1 actions) + activate eosinophils + mast cells
- promote strong Ab response based on neutralising IgG + IgE
What is the role of mast cells in extracellular immunity?
- Early response- sentinel function, produce alarmin, initiation/ amplification of Th2 response
- Later response- expand + become activated in response to IL-9, express receptor for Fc region of IgE, degranulate wen IgE bound to Fc receptors on mast cell surface interacts w/ Ag, released of histamine/ proteases/ cytokines
What is the role of eosinophils in extracellular immunity?
- IL-5 drives accumulation of eosinophils in blood + tissues
- express high affinity receptor for Fc region of IgE
- IgE binds to surface of helminths- eosinophils bind to Fc region = degranulation of eosinophils = destruction of helminth cuticle
Describe some helminth evasion tactics
- think extracellular coat
- absorbing host proteins (masks Ags)
- Molecular mimicry
- Anatomical seclusion
- Surface Ag shedding
- Migration
How do Th2 cells promote neutralising Abs?
- Th2 cells suppress activation of macrophages + promote a strong Ab response based on neutralising IgGs
What does Ab mediated protection against extracellular bacteria do?
neutralises toxins, kills bacteria, opsonises bacteria, intracellular killing by macrophages, essential protection for neonates
